Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the U.S. with yearly treatment costs estimated to be near $8 billion. The increasing amount of research on bioactives and functional foods has fueled the development and marketing of foods and dietary supplements for prostate health, including both soy and tomato phytochemicals, and men may consume combinations of these products. However, it can't be assumed that combinations of supplements and functional foods will be more effective, and it is important to identify interactions that could alter the efficacy or safety of dietary interventions. The long range goal of the proposed research is to quantitatively define and understand the mechanisms by which consumption of soy or tomato products may reduce the risk of PCa. The objective of this application is to investigate the effects of soy germ and/or tomato powder containing diets on the progression of PCa in a transgenic adenocarcinoma of mouse prostate (TRAMP) model. In parallel, we will investigate the bioavailability of tomato carotenoids and soy isoflavones when tomato and soy germ are consumed together. To answer the questions raised in this proposal, diets containing 2% soy germ and/or 10% tomato powder will be fed to TRAMP mice prior to puberty and throughout progression of carcinogenesis. The specific aims for this proposal are 1) To investigate the effects of tomato and/or soy germ containing diets on progression of prostate carcinogenesis and identify their anticarcinogenic mechanisms of action in TRAMP mice 2) To measure bioavailability of tomato carotenoids and soy germ isoflavones in TRAMP mice. It is hypothesized that consumption of soy germ or tomato will reduce the incidence of poorly-differentiated carcinoma, and the combination of the two will not be as effective as when consumed individually. Potential anticarcinogenic mechanisms of the dietary interventions will be investigated through cancer pathway findway PCR arrays and immunohistochemistry. It is hypothesized that an interaction between soy germ and tomato alters bioactive bioavailability. Carotenoid bioaccumulation, serum lycopene metabolites, and urinary isoflavones will be measured to determine if combined consumption alters bioavailability of these bioactives and if the alteration correlates with how soy germ and/or tomato powder modulate prostate carcinogenesis. The proposed research is a unique approach to understand the efficacy of dietary interventions for PCa prevention. We will use whole foods rather than isolated bioactives and investigate a combination of foods to identify potential interactions. The research will benefit both consumers of supplements and the scientific community by providing a better understanding of the safety and efficacy of dietary interventions as alternative strategies for PCa prevention. PUBLIC HEALTH RELEVANCE: Utilizing dietary approaches to reduce the risk or delay the onset of prostate cancer (PCa) would have a profound impact on public health and health care costs. The proposed research will investigate the efficacy of dietary soy germ and/or tomato for prevention of PCa, potentially identifying safe and cost-effective prevention strategies.